Studies will be performed on hepatocytes isolated from fed rats to determine the patterns of carbon flow in the pentose phosphate pathway and the glycolytic and glycogenic pathways. Cells will be incubated with a mixture of glucose, mannose, ribose, glycerol, and acetate, with only one of these substrates in any given incubation labeled with 14C in a specified atom. Measurements will be made of label incorporation in CO2, glucose, lipids, and glycogen, and the data will be analyzed with the aid of a computer model of the metabolic pathways. Similar experiments will be initiated using hepatocytes from fasted rats, incubated in the presence and absence of glucagon. These experiments should allow one to compare the amount of "futile" cycling at several substrate cycles in the fed and fasted rat (for this particular substrate mixture) and to assess the effects of glucagon on metabolite flow in these pathways. Similar studies on the ciliated protozoan Tetrahymena pyriformis have led to the discovery that calmodulin is present in this cell and that glycogen metabolism is perturbed by chlorpromazine, perhaps in part because of a loss of amino acid transport capacity. The effects of chlorpromazine on the intermediary metabolism of Tetrahymena will be further examined, using substrate mixtures which have proven useful in the analysis of metabolite flux patterns in this cell.